In heart muscle, as in other tissues required to sustain continued high levels of work output, the energy transduction processes occurring in the inner mitochondrial membrane are vital to tissue health. Cytochrome c, the one protein component of the mitochondrial terminal respiratory chain which is readily obtainable from heart tissue in pure form, plays a central role in such processes. Even though a wealth of information is available concerning its action kinetics with other respiratory chain components, its amino acid sequence and its spatial structure, effective protein molecular details of overall functional activities are lacking, precluding an understanding of mechanisms and thereby precluding any possibility of their control. The precise definition of the differences in structure between the two oxidation states makes it possible to obtain specific derivatives of the protein and develop chemical, immunological and other experiments to determine the molecular mechanism of oxidoreduction, to identify oxidase and reductase binding and reaction sites, as well as membrane-binding sites, to establish whether cytochrome c is or is not involved in a direct way in oxidative phosphorylation and in other possible metabolic functions involving ion-binding. The program will be carried out with detailed comparisons of the same reactions in membranes and in soluble systems to determine the specific effects of the membrane environment. This is expected to lead to an understanding of the physiological regulation of cytochrome c function. Bibliographic references: E. Margoliash. The molecular variations of cytochrome c as a function of the evolution of species. Adv. Chem. Phys., 29, 191-252 (1975). S. Ferguson-Miller, C. H. Kang and E. Margoliash. Kinetics of respiratory chain electron transfer activities of cytochromes c of different species. Federation Proc., 34 (1975).